Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts

Abstract

Our results indicate that in the isolated rabbit heart, landiolol and esmolol had equipotent negative chronotropic effects, however, landiolol had a less potent negative inotropic effect than esmolol.

Direct Effects of Esmolol and Landiolol on Cardiac Function, Coronary Vasoactivity, and Ventricular Electrophysiology in Guinea-Pig Hearts

“…Therefore, it is postulated that the negative inotropic effect (NIE) of esmolol is, at least in part, the result of shortening of the action potential. In contrast to esmolol, landiolol had no apparent effects on the action potential or ionic currents of ventricular myocytes, consistent with the findings of previous studies (7,9,10,13). Furthermore, the NIE of esmolol, but not of landiolol, has also been reported in previous studies; for example, Ikeshita et al (9) reported that esmolol induces strikingly dose-dependent negative inotropic effects, at 1 -10 μM, and almost completely abolished contraction in the rabbit heart at 100 μM.…”

“…Furthermore, the NIE of esmolol, but not of landiolol, has also been reported in previous studies; for example, Ikeshita et al (9) reported that esmolol induces strikingly dose-dependent negative inotropic effects, at 1 -10 μM, and almost completely abolished contraction in the rabbit heart at 100 μM. They suggested the actions of esmolol are largely due to its β-blocking effects (9). Further increasing the dose of esmolol to 1.0 mM has previously been shown to induce cardiac arrest (14), indicating its potency.…”

“…Several independent studies comparing the negative chronotropic and inotropic effects of esmolol and landiolol revealed that esmolol had greater negative inotropic potency than landiolol (7 -9); however, the mechanisms underlying the disparity in negative inotropic potency between the two drugs are currently unknown. The majority of these comparative studies were conducted with sympathetic stimulation (9,10), and hence the direct effects of these drugs on cardiac function are undefined. Ikeshita et al (9) showed that when esmolol was applied cumulatively to isolated rabbit heart in the presence of isoproterenol, it produced significant negative inotropic action.…”

“…The majority of these comparative studies were conducted with sympathetic stimulation (9,10), and hence the direct effects of these drugs on cardiac function are undefined. Ikeshita et al (9) showed that when esmolol was applied cumulatively to isolated rabbit heart in the presence of isoproterenol, it produced significant negative inotropic action. They also noted that both left ventricular developed pressure and the maximal rate of left ventricular force development were reduced to levels less than the baseline (in the absence of isoproterenol and esmolol) value.…”

Do we need an individual approach to atrial fibrillation and adrenergic overload in the critically ill?

“…In our opinion, the extreme caution in patient selection based on echocardiografically determined preserved systolic and impaired diastolic left/right ventricular function and very low initial dose of ultra-selective β1-blocker is necessary so as not to induce harm to the critically ill septic patient. (50) In the future, it will probably be important even to determine the pharmacogenetic profile of β-AR in these patients. Critical illness and management in a critical care unit are characterised by a severe and abnormally prolonged stressor response; this response may become maladaptive.…”